Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
Laboratory Animal Resource Center, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
Nat Commun. 2017 Nov 22;8(1):1700. doi: 10.1038/s41467-017-01711-0.
The transcription factor MafB is expressed by monocytes and macrophages. Efferocytosis (apoptotic cell uptake) by macrophages is important for inhibiting the development of autoimmune diseases, and is greatly reduced in Mafb-deficient macrophages. Here, we show the expression of the first protein in the classical complement pathway C1q is important for mediating efferocytosis and is reduced in Mafb-deficient macrophages. The efferocytosis defect in Mafb-deficient macrophages can be rescued by adding serum from wild-type mice, but not by adding serum from C1q-deficient mice. By hemolysis assay we also show that activation of the classical complement pathway is decreased in Mafb-deficient mice. In addition, MafB overexpression induces C1q-dependent gene expression and signals that induce C1q genes are less effective in the absence of MafB. We also show that Mafb-deficiency can increase glomerular autoimmunity, including anti-nuclear antibody deposition. These results show that MafB is an important regulator of C1q.
转录因子 MafB 由单核细胞和巨噬细胞表达。巨噬细胞的吞噬作用（凋亡细胞摄取）对于抑制自身免疫性疾病的发展非常重要，而在 Mafb 缺陷型巨噬细胞中，吞噬作用大大减少。在这里，我们表明经典补体途径中的第一个蛋白 C1q 的表达对于介导吞噬作用很重要，并且在 Mafb 缺陷型巨噬细胞中减少。Mafb 缺陷型巨噬细胞中的吞噬作用缺陷可以通过添加来自野生型小鼠的血清来挽救，但不能通过添加来自 C1q 缺陷型小鼠的血清来挽救。通过溶血测定，我们还表明经典补体途径的激活在 Mafb 缺陷型小鼠中降低。此外，MafB 的过表达诱导 C1q 依赖性基因表达，并且在没有 MafB 的情况下，诱导 C1q 基因的信号不太有效。我们还表明，Mafb 缺陷可增加肾小球自身免疫，包括抗核抗体沉积。这些结果表明 MafB 是 C1q 的重要调节剂。
